Altered drug translocation mediated by the MDR protein: Direct,indirect, or both?

Overexpression of the MDR protein, or p-glycoprotein (p-GP), in cells leads to decreased initial rates of accumulation and altered intracellular retention of chemotherapeutic drugs and a variety of other compounds. Thus, increased expression of the protein is related to increased drug resistance. Since several homologues of the MDR protein (CRP, ltpGPA, PDR5, sapABCDF) are also involved in conferring drug resistance phenomena in microorganisms, elucidating the function of the MDR protein at a molecular level will have important general applications. Although MDR protein function has been studied for nearly 20 years, interpretation of most data is complicated by the drug-selection conditions used to create model MDR cell lines. Precisely what level of resistance to particular drugs is conferred by a given amount of MDR protein, as well as a variety of other critical issues, are not yet resolved. Data from a number of laboratories has been gathered in support of at least four different models for the MDR protein. One model is that the protein uses the energy released from ATP hydrolysis to directly translocate drugs out of cells in some fashion. Another is that MDR protein overexpression perturbs electrical membrane potential () and/or intracellular pH (pH_i) and therebyindirectly alters translocation and intracellular retention of hydrophobic drugs that are cationic, weakly basic, and/or that react with intracellular targets in a pH_i, or -dependent manner. A third model proposes that the protein alternates between drug pump and Cl^– channel (or channel regulator) conformations, implying that both direct and indirect mechanisms of altered drug translocation may be catalyzed by MDR protein. A fourth is that the protein acts as an ATP channel. Our recent work has tested predictions of these models via kinetic analysis of drug transport and single-cell photometry analysis of pH_i, , and volume regulation in novel MDR and CFTR transfectants that have not been exposed to chemotherapeutic drugs prior to analysis. This paper reviews these data and previous work from other laboratories, as well as relevant transport physiology concepts, and summarizes how they either support or contradict the different models for MDR protein function.     

锈寄生菌对落叶松褐锈病的抑制效应

目测及镜检结果表明,褐锈菌被锈寄生菌寄生后,夏孢子堆由桔红渐变为灰褐,后期夏孢子失去发芽力,孢子堆原基处只存有寄生菌的分生孢子器．锈寄生菌的发酵液代谢产物含有３种抗性物质．自７月中下旬至９月中旬,分生孢子的发生量多于褐锈菌的孢子量,表明落叶松褐锈病的发生程度随着锈寄生菌寄生率的增加而减轻．     

精制白喉毒素加β—丙氨酸后脱毒效果观察

精制白喉毒素加０．０２Ｍβ—丙氨酸,再加甲醛溶液经适当的时间解毒,即可转化为完全类毒化且无毒性逆转的精制白喉类毒素。此精白类的脱毒试验、毒性逆转试验、安全试验及效力试验均符合《中国生物制品规程》要求。在脱毒过程中絮状单位的损失明显低于单纯甲醛脱毒者,纯度亦相应得到了提高。     

人粒细胞集落刺激因子（hG－CSF）cDNA3′－UTR对其表达的影响

利用人粒细胞集落刺激因子（ｈＧ－ＣＳＦ）ｃＤＮＡ３′端非翻译区（３′－ＵＴＲ）中存在的ＤｒａⅠ酶切位点,通过部分酶切与完全酶切,删除３′－ＵＴＲ不同长度,构建了四种ｈＧ－ＣＳＦｃＤＮＡ瞬时重组表达质粒。转染ＣＯＳ－７细胞后,生物活性测定结果提示,ｈＧ－ＣＳＦｃＤＮＡ３′－ＵＴＲ对其表达起负调控作用,其关键性序列位于紧接终止密码子ＴＧＡ下游的６５ｂｐ范围内,３′－ＵＴＲ对ｈＧ－ＣＳＦｃＤＮＡ表达的影响与转录水平的差别有一定关系。     

Epipolarization Microscopic Immunogold Assay: a Combination of Immunogold Silver Staining, Enzyme-Linked-Immunosorbent Assay and Epipolarization Microscopy

We describe a new immunoassay which combines an immunosorbent assay, Immunogold silver staining and epipolarization microscopy. Our new assay procedure features multiple samples on a single microscope slide, and high sensitivity of epipolarization microscope for detection of silver-enhanced colloidal gold as a final immunoassay product. We call the new immunoassay “on slide immunogold assay” (OSIGA). This new method uses biotinylated antibody and streptavidin-gold reaction with silver enhancement technique. With OSIGA it is possible to investigate 30 samples on a single microscopic slide. Our preliminary studies used 10-20 μ1 samples and detected nanogram quantities of a standardized protein solution. Unlike enzyme linked immunosorbent assay (ELISA), which has a limited time for reading the final color products, the OSIGA specimens can be dried or resin mounted for longer storage and future reference.     

广西崇左县冲塘新石器时代人骨微量元素的初步研究

本文对广西崇左县冲塘新石器时代的３个个体（Ｍ０２,Ｓ０８,Ｓ０９）的肢骨进行了化学元素（Ｓｒ,Ｚｎ,Ｃａ,Ｐ,Ｃｄ,Ｐｈ）的含量测定．并根据研究结果对当时人类的生活环境、食物性质作了推测和分析．     

几种CAM植物PEP羧化酶同工酶的比较研究

比较研究几种兼性和专一性ＣＡＭ植物材料的ＰＥＰＣ同工酶表明：经自然干旱诱导,兼性ＣＡＭ植物露花（Ｍｅｓｅｍｂｒｙａｎｔｈｅｍｕｍｃｏｒｄｉｆｏｌｉｕｍ）、长药景天（Ｓｕｄｕｍｓｐｅｃｔａｂｉｌｅ）有新的ＰＥＰＣ同工酶的出现,诱导前后各同工酶的天然分子量变化不大;而土三七（Ｓｅｄｕｍａｉｚｏｏｎ）则没有新的ＰＥＰＣ同工酶出现,但诱导后其同工酶的天然分子量有所增大。以上几种兼性ＣＡＭ植物的ＰＥＰＣ同工酶酶谱无明显昼夜变化。专一性ＣＡＭ植物的ＰＥＰＣ酶谱和天然分子量均较一致,亦无昼夜差异。     

腺苷转运体亲和层析分离

本文合成了一种腺苷亲和层析凝胶,并采用亲和层析法从牛脑细胞膜上分离出了几种膜上结合的腺苷结合蛋白质。这些蛋白质在ＳＤＳ－ＰＡＧＥ电泳凝胶上为单一或主要的蛋白带,分子量分别为６４ｋｄ,４５ｋｄ,３５ｋｄ。腺苷转运体抑制剂潘生丁和ＮＢＭＰＲ对６４ｋｄ蛋白与＾３ｈ－腺苷的结合抑制作用远强于腺苷受体的激动剂ＮＥＣＡ和Ｒ－ＰＩＡ;这表明６４ｋｄ蛋白为牛脑细胞膜上结合的腺苷转运体。     

尼群地平对实验性糖尿病大鼠心肌收缩性的影响

腹腔注射链脲佐霉素（６５ｍｇ／ｋｇ）诱发Ｗｉｓｔａｒ大鼠糖尿病。糖尿病发病４周后,向饲料中加尼群地平（３０ｍｇ·ｋｇ－１·ｄ－１）。结果表明,糖尿病４周时大鼠心室舒张功能首先受损,８周后心室舒张和收缩功能均明显受累。尼群地平处理对糖尿病大鼠的心肌收缩性有一定的改善作用。提示尼群地平对大鼠糖尿病性心肌病有一定有益作用。